Sulfhydryl groups of the erythrocyte membrane and their relation to glycolysis and drug induced hemolytic anemia

Abstract

A sulfhydryl group involved in membrane structure, dependent on intracellular metabolism for maintenance of the reduced state is described. It is postulated that this metabolically dependent membrane sulfhydryl group may play a role in the pathogenesis of drug induced hemolytic anemia. Membrane sulfhydryl groups were studied by observing the effect of sulfhydryl blocking agents, e.g. N ethylmaleimide (NEM), on the recovery of erythrocyte ghosts after osmotic lysis. It was shown that NEM interfered with ghost recovery by reacting with membrane sulfhydryl groups. The concentration of NEM (as determined by [14C]NEM binding) necessary to cause this effect was lower than that necessary to produce changes in osmotic fragility or cation permeability, or to cause Heinz body formation. In the absence of glucose, these sulfhydryl groups became disulfides, but could be returned to the reduced state by restoring glycolysis or by adding dithiothreitol. Phenylhydrazine hemolytic anemia was induced in pigs, and membrane changes of the type described above occurred early in the pathogenesis of the disease.